Activation of NF-kB signaling is a critical event downstream of CLEC7A (Dectin-1), CLEC6A (Dectin-2) (Bi et al. 2010) and CLEC4E (Mincle) (Yamasaki et al. 2008), requiring the adapter protein Caspase recruitment domain (CARD)-containing protein 9 (CARD9) in dendritic cells and in macrophages (Gross et al. 2006, Hara et al. 2007). CARD9 is analogous to CARD-containing MAGUK protein 1 (CARMA1), which mediates T-cell receptor (TCR) activation of NF-kB in lymphocytes. CARD9 is downstream of SYK and becomes phosphorylated by PRKCD (Protein kinase C-delta) phosphorylates CARD9 on Thr-231 (T231), which is required for the signal-induced association of CARD9 with B-cell lymphoma 10 (BCL10) and Mucosa-associated lymphoid tissue 1 (MALT1) and the subsequent recruitment of MAP3K transforming growth factor beta activated kinase 1 (TAK1), leading to activation of the NF-kB pathway (Strasser et al. 2012). A homozygous loss-of-function mutation in human CARD9 results in a premature termination codon (Gln295*). Patients with this mutation are highly susceptible to fungal infections (Glocker et al. 2009).
Strasser, D, Neumann, K, Bergmann, H, Marakalala, MJ, Guler, R, Rojowska, A, Hopfner, KP, Brombacher, F, Urlaub, H, Baier, G, Brown, GD, Leitges, M, Ruland, J
calcium-independent protein kinase C activity of DAGs:active p-T507,S645,S664-PRKCD [plasma membrane]
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